The landscape of somatic mutation in normal colorectal epithelial cells
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Abstract
The colorectal adenoma-carcinoma sequence has provided a paradigmatic framework for understanding the successive somatic genetic changes and consequent clonal expansions that lead to cancer 1. However, our understanding of the earliest phases of colorectal neoplastic changes-which may occur in morphologically normal tissue-is comparatively limited, as for most cancer types. Here we use whole-genome sequencing to analyse hundreds of normal crypts from 42 individuals. Signatures of multiple mutational processes were revealed; some of these were ubiquitous and continuous, whereas others were only found in some individuals, in some crypts or during certain periods of life. Probable driver mutations were present in around 1% of normal colorectal crypts in middle-aged individuals, indicating that adenomas and carcinomas are rare outcomes of a pervasive process of neoplastic change across morphologically normal colorectal epithelium. Colorectal cancers exhibit substantially increased mutational burdens relative to normal cells. Sequencing normal colorectal cells provides quantitative insights into the genomic and clonal evolution of cancer.
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Cancer research suggests that colibactin causes DNA damage early after exposure.
“cancer research suggests that colibactin causes DNA damage early after exposure [157, 158].”
From Selection, Comparative Genomics, and Potential Probiotic Features of Escherichia coli 5C, a pks-Negative Strain Isolated from Healthy Infant Donor Feces (2026) · cites this paper as [157]
The Sporadic mutational signatures section (p. 4) describes an early-life mutational process but says its initiating event is unknown. A search for colibactin found no passage in our copy linking it to DNA damage or establishing how soon damage occurs after exposure. (LLM, conf=0.75)
Experimental — accuracy not yet measuredClonal expansion has also been found in other human tissues, including skin, colon and oesophagus, and is thought to be a normal, possibly ubiquitous, process associated with ageing in all tissues, in particular those that experience significant cellular turnover.
“Clonal expansion has also been found in other human tissues, including skin, colon and oesophagus52–54, and is thought to be a normal, possibly ubiquitous, process that is associated with ageing in all tissues, in particular those that experience significant cellular turnover.”
From Ageing and rejuvenation of tissue stem cells and their niches (2023) · cites this paper as [52]
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PHYLIP-Phylogeny inference package (Version 3.2)
Felsenstein, J. (1989) · Cladistics · Cited by 17,848 · see citing works
ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data
Wang, K., Li, M., & Hakonarson, H. H. (2010) · Nucleic Acids Research · doi:10.1093/nar/gkq603 · Cited by 14,380 · see citing works
A genetic model for colorectal tumorigenesis
Fearon, E. R., & Vogelstein, B. (1990) · Cell · doi:10.1016/0092-8674(90)90186-i · Cited by 12,132 · see citing works
Signatures of mutational processes in human cancer
Initiative, A. P. C. G., Alexandrov, L. B., ICGC Breast Cancer Consortium, ICGC MMML-Seq Consortium, PedBrain, I., Nik-Zainal, S., Wedge, D. C., Aparicio, S. A. J. R., Behjati, S., Biankin, A. V., et al. (2013) · Nature · doi:10.1038/nature12477 · Cited by 9,660 · see citing works
Self-citationComprehensive molecular characterization of human colon and rectal cancer
The Cancer Genome Atlas Network (2012) · Nature · doi:10.1038/nature11252 · Cited by 8,499 · see citing works
Age-related clonal hematopoiesis associated with adverse outcomes
Jaiswal, S., Fontanillas, P., Flannick, J., Manning, A., Grauman, P. V., Mar, B. G., Lindsley, R. C., Mermel, C. H., Burtt, N., Chavez, A., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1408617 · Cited by 4,841 · see citing works
Clonal hematopoiesis and blood-cancer risk inferred from blood DNA sequence
Genovese, G., Kähler, A. K., Handsaker, R. E., Lindberg, J., Rose, S. A., Bakhoum, S. F., Chambert, K., Mick, E., Neale, B. M., Fromer, M., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1409405 · Cited by 3,531 · see citing works
Crypt stem cells as the cells-of-origin of intestinal cancer
Barker, N., Ridgway, R. A., van Es, J. H., van de Wetering, M., Begthel, H., van den Born, M., Danenberg, E., Clarke, A. R., Sansom, O. J., & Clevers, H. C. (2008) · Nature · doi:10.1038/nature07602 · Cited by 2,159 · see citing works
Snippert, H. J., van der Flier, L. G., Sato, T., van Es, J. H., van den Born, M., Kroon-Veenboer, C., Barker, N., Klein, A. M., van Rheenen, J., Simons, B. D., et al. (2010) · Cell · doi:10.1016/j.cell.2010.09.016 · Cited by 1,951 · see citing works
COSMIC: somatic cancer genetics at high-resolution
Forbes, S. A., Beare, D., Boutselakis, H., Bamford, S., Bindal, N., Tate, J., Cole, C. G., Ward, S., Dawson, E., Ponting, L., et al. (2017) · Nucleic Acids Research · doi:10.1093/nar/gkw1121 · Cited by 1,922 · see citing works
Self-citationMutational Processes Molding the Genomes of 21 Breast Cancers
Nik-Zainal, S., Alexandrov, L. B., Wedge, D. C., Van Loo, P., Greenman, C. D., Raine, K., Jones, D., Hinton, J., Marshall, J., Stebbings, L. A., et al. (2012) · Cell · doi:10.1016/j.cell.2012.04.024 · Cited by 1,909 · see citing works
Self-citationAge-related mutations associated with clonal hematopoietic expansion and malignancies
Xie, M., Lu, C., Wang, J., McLellan, M. D., Johnson, K. J., Wendl, M. C., McMichael, J. F., Schmidt, H. K., Yellapantula, V., Miller, C. A., et al. (2014) · Nature Medicine · doi:10.1038/nm.3733 · Cited by 1,874 · see citing works
Self-citationHigh burden and pervasive positive selection of somatic mutations in normal human skin
Martincorena, I., Roshan, A., Gerstung, M., Ellis, P., Van Loo, P., McLaren, S., Wedge, D. C., Fullam, A., Alexandrov, L. B., Tubio, J. M., et al. (2015) · Science · doi:10.1126/science.aaa6806 · Cited by 1,770 · see citing works
Self-citationCheng, H., & Leblond, C. P. (1974) · American Journal of Anatomy · doi:10.1002/aja.1001410407 · Cited by 1,737 · see citing works
The origin and evolution of mutations in acute myeloid leukemia
Welch, J. S., Ley, T. J., Link, D. C., Miller, C. A., Larson, D. E., Koboldt, D. C., Wartman, L. D., Lamprecht, T. L., Liu, F., Xia, J., et al. (2012) · Cell · doi:10.1016/j.cell.2012.06.023 · Cited by 1,575 · see citing works
Universal Patterns of Selection in Cancer and Somatic Tissues
Martincorena, I., Raine, K. M., Gerstung, M., Dawson, K. J., Haase, K., Van Loo, P., Davies, H., Stratton, M. R., & Campbell, P. J. (2017) · Cell · doi:10.1016/j.cell.2017.09.042 · Cited by 1,523 · see citing works
Self-citationAllele-specific copy number analysis of tumors
Loo, P. V., Nord, S., Lingjærde, O. C., Russnes, H. G., Rye, I. H., Sun, W., Weigman, V., Marynen, P., Zetterberg, A., Naume, B., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1009843107 · Cited by 1,231 · see citing works
Somatic mutant clones colonize the human esophagus with age
Martincorena, I., Fowler, J. C., Wabik, A., Lawson, A. R. J., Abascal, F., Hall, M. W. J., Cagan, A., Murai, K., Mahbubani, K., Stratton, M. R., et al. (2018) · Science · doi:10.1126/science.aau3879 · Cited by 1,113 · see citing works
Self-citationTissue-specific mutation accumulation in human adult stem cells during life
Blokzijl, F., de Ligt, J., Jager, M., Sasselli, V., Roerink, S., Sasaki, N., Huch, M., Boymans, S., Kuijk, E., Prins, P., et al. (2016) · Nature · doi:10.1038/nature19768 · Cited by 935 · see citing works
Self-citationJBrowse: a dynamic web platform for genome visualization and analysis
Buels, R., Yao, E., Diesh, C. M., Hayes, R. D., Muñoz-Torres, M. C., Helt, G. A., Goodstein, D. M., Elsik, C. G., Lewis, S., Stein, L. D., et al. (2016) · Genome biology · doi:10.1186/s13059-016-0924-1 · Cited by 742 · see citing works
Intestinal Stem Cell Replacement Follows a Pattern of Neutral Drift
López‐García, C., Klein, A. M., Simons, B. D., & Winton, D. J. (2010) · Science · doi:10.1126/science.1196236 · Cited by 646 · see citing works
Aging and neurodegeneration are associated with increased mutations in single human neurons
Lodato, M. A., Rodin, R. E., Bohrson, C. L., Coulter, M. E., Barton, A. R., Kwon, M., Sherman, M. A., Vitzthum, C. M., Luquette, L. J., Yandava, C. N., et al. (2018) · Science · doi:10.1126/science.aao4426 · Cited by 635 · see citing works
Population dynamics of normal human blood inferred from somatic mutations
Lee-Six, H., Øbro, N. F., Shepherd, M. S., Grossmann, S., Dawson, K., Belmonte, M., Osborne, R. J., Huntly, B. J. P., Martincorena, I., Anderson, E., et al. (2018) · Nature · doi:10.1038/s41586-018-0497-0 · Cited by 604 · see citing works
Self-citationIntra-tumour diversification in colorectal cancer at the single-cell level
Roerink, S. F., Sasaki, N., Lee-Six, H., Young, M. D., Alexandrov, L. B., Behjati, S., Mitchell, T. J., Großmann, S., Lightfoot, H. W., Egan, D. A., et al. (2018) · Nature · doi:10.1038/s41586-018-0024-3 · Cited by 554 · see citing works
Self-citationLeukemia-associated somatic mutations drive distinct patterns of age-related clonal hemopoiesis
McKerrell, T., Park, N., Moreno, T., Grove, C. S., Ponstingl, H., Stephens, J., Crawley, C., Craig, J., Scott, M. A., Hodkinson, C., et al. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.02.005 · Cited by 534 · see citing works
The Repertoire of Mutational Signatures in Human CancerPreprint
Alexandrov, L. B., Kim, J., Haradhvala, N. J., Huang, M. N., Ng, A. W. T., Wu, Y., Boot, A., Covington, K. R., Gordenin, D. A., Bergstrom, E. N., et al. (2018) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/322859 · Cited by 529 · see citing works
Self-citationThe mutational landscape of normal human endometrial epithelium
Moore, L., Leongamornlert, D., Coorens, T. H. H., Sanders, M. A., Ellis, P., Dentro, S. C., Dawson, K. J., Butler, T., Rahbari, R., Mitchell, T. J., et al. (2020) · Nature · doi:10.1038/s41586-020-2214-z · Cited by 499 · see citing works
Self-citationScheinin, I., Sie, D., Bengtsson, H. L., van de Wiel, M. A., Olshen, A. B., van Thuijl, H. F., Essen, H. F. H. V., Eijk, P. P., Rustenburg, F., Meijer, G. A., et al. (2014) · Genome Research · doi:10.1101/gr.175141.114 · Cited by 491 · see citing works
Chan, K., Roberts, S. A., Klimczak, L. J., Sterling, J. F., Saini, N., Malc, E. P., Kim, J., Kwiatkowski, D. J., Fargo, D. C., Mieczkowski, P. A., et al. (2015) · Nature Genetics · doi:10.1038/ng.3378 · Cited by 414 · see citing works
Suda, K., Nakaoka, H., Yoshihara, K., Ishiguro, T., Tamura, R., Mori, Y., Yamawaki, K., Adachi, S., Takahashi, T., Kase, H., et al. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.07.037 · Cited by 414 · see citing works
Mutational Strand Asymmetries in Cancer Genomes Reveal Mechanisms of DNA Damage and Repair
Haradhvala, N. J., Polak, P. P., Stojanov, P., Covington, K. R., Shinbrot, E., Hess, J. M., Rheinbay, E., Kim, J., Maruvka, Y. E., Braunstein, L. Z., et al. (2016) · Cell · doi:10.1016/j.cell.2015.12.050 · Cited by 387 · see citing works
Genome sequencing of normal cells reveals developmental lineages and mutational processes
Behjati, S., Huch, M., van Boxtel, R., Karthaus, W., Wedge, D., Tamuri, A. U., Martincorena, I., Petljak, M., Alexandrov, L., Gundem, G., et al. (2014) · Nature · doi:10.1038/nature13448 · Cited by 342 · see citing works
Self-citationDifferent mutational rates and mechanisms in human cells at pregastrulation and neurogenesis
Bae, T., Tomasini, L., Mariani, J., Zhou, B., Roychowdhury, T., Franjic, D., Pletikos, M., Pattni, R., Chen, B.-J., Venturini, E., et al. (2017) · Science · doi:10.1126/science.aan8690 · Cited by 259 · see citing works
Corley, D. A., Jensen, C. D., Marks, A. R., Zhao, W. K., de Boer, J., Levin, T. R., Doubeni, C. A., FIREMAN, B. H., & Quesenberry, C. P. (2012) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2012.09.010 · Cited by 242 · see citing works
Jones, D., Raine, K. M., Davies, H. R., Tarpey, P. S., Butler, A. P., Teague, J. W., Nik‐Zainal, S., & Campbell, P. J. (2016) · Current Protocols in Bioinformatics · doi:10.1002/cpbi.20 · Cited by 227 · see citing works
Self-citationEstimating telomere length from whole genome sequence data
Ding, Z., Mangino, M., Aviv, A., Spector, T. D., & Durbin, R. M. (2014) · Nucleic Acids Research · doi:10.1093/nar/gku181 · Cited by 224 · see citing works
Hoang, M. L., Kinde, I., Tomasetti, C., McMahon, K. W., Rosenquist, T. A., Grollman, A. P., Kinzler, K. W., Vogelstein, B., & Papadopoulos, N. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1607794113 · Cited by 224 · see citing works
Measurement of in vivo proliferation in human colorectal mucosa using bromodeoxyuridine.
Potten, C. S., Kellett, M., Roberts, S. A., Rew, D. A., & Wilson, G. D. (1992) · Gut · doi:10.1136/gut.33.1.71 · Cited by 219 · see citing works
Viel, A., Bruselles, A., Meccia, E., Fornasarig, M., Quaia, M., Canzonieri, V., Policicchio, E., Urso, E. D., Agostini, M., Genuardi, M., et al. (2017) · EBioMedicine · doi:10.1016/j.ebiom.2017.04.022 · Cited by 217 · see citing works
Kozar, S., Morrissey, E., Nicholson, A. M., van der Heijden, M., Zecchini, H. I., Kemp, R., Tavaré, S., Vermeulen, L., & Winton, D. J. (2013) · Cell Stem Cell · doi:10.1016/j.stem.2013.08.001 · Cited by 214 · see citing works
Wolf, J., Kapp, U., Bohlen, H., et al. (1996) · Blood · doi:10.1182/blood.v87.8.3418.bloodjournal8783418 · Cited by 185 · see citing works
Stem-cell organization in mouse small intestine
Winton, D. J., & Ponder, B. A. J. (1990) · Proceedings of the Royal Society B Biological Sciences · doi:10.1098/rspb.1990.0059 · Cited by 176 · see citing works
Demonstration of somatic mutation and colonic crypt clonality by X-linked enzyme histochemistry
Griffiths, D. F. R., Davies, S. J., Williams, D. W., Williams, G., & Williams, E. D. (1988) · Nature · doi:10.1038/333461a0 · Cited by 170 · see citing works
Therapy-associated Solid Tumors
Travis, L. B. (2002) · Acta Oncologica · doi:10.1080/028418602760169361 · Cited by 164 · see citing works
cgpPindel: Identifying Somatically Acquired Insertion and Deletion Events from Paired End Sequencing
Raine, K. M., Hinton, J., Butler, A. P., Teague, J. W., Davies, H. R., Tarpey, P. S., Nik‐Zainal, S., & Campbell, P. J. (2015) · Current Protocols in Bioinformatics · doi:10.1002/0471250953.bi1507s52 · Cited by 141 · see citing works
Self-citationThe landscape of somatic mutation in normal colorectal epithelial cellsPreprint
Lee-Six, H., Ellis, P., Osborne, R. J., Sanders, M. A., Moore, L., Georgakopoulos, N., Torrente, F., Noorani, A., Goddard, M. J., Robinson, P. S., et al. (2018) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/416800 · Cited by 128 · see citing works
Self-citationTelomereHunter – in silico estimation of telomere content and composition from cancer genomes
Feuerbach, L., Sieverling, L., Deeg, K. I., Ginsbach, P., Hutter, B., Buchhalter, I., Northcott, P. A., Mughal, S. S., Chudasama, P., Glimm, H., et al. (2019) · BMC Bioinformatics · doi:10.1186/s12859-019-2851-0 · Cited by 123 · see citing works
Fixation and Spread of Somatic Mutations in Adult Human Colonic Epithelium
Nicholson, A. M., Olpe, C., Hoyle, A., Thorsen, A.-S., Rus, T., Colombé, M., Brunton-Sim, R., Kemp, R., Marks, K., Quirke, P., et al. (2018) · Cell stem cell · doi:10.1016/j.stem.2018.04.020 · Cited by 116 · see citing works
Mutational History of a Human Cell Lineage from Somatic to Induced Pluripotent Stem Cells
Rouhani, F. J., Nik‐Zainal, S., Wüster, A., Li, Y., Conte, N., Koike-Yusa, H., Kumasaka, N., Vallier, L., Yusa, K., & Bradley, A. (2016) · PLoS Genetics · doi:10.1371/journal.pgen.1005932 · Cited by 112 · see citing works
The mutational landscape of normal human endometrial epitheliumPreprint
Moore, L., Leongamornlert, D. A., Coorens, T. H. H., et al. (2018) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/505685 · Cited by 107 · see citing works
Self-citationFrequent occurrence of uniparental disomy in colorectal cancer
Andersen, C. L., Wiuf, C., Kruhøffer, M., Korsgaard, M., Laurberg, S., & Orntoft, T. F. (2006) · Carcinogenesis · doi:10.1093/carcin/bgl086 · Cited by 105 · see citing works
Farmery, J. H. R., Smith, M. L., Diseases, N. B. R., Huissoon, A. P., Furnell, A., Mead, A. J., Levine, A. P., Manzur, A. Y., Thrasher, A. J., Greenhalgh, A. J., et al. (2018) · Scientific Reports · doi:10.1038/s41598-017-14403-y · Cited by 88 · see citing works
Computel: Computation of Mean Telomere Length from Whole-Genome Next-Generation Sequencing Data
Nersisyan, L., & Arakelyan, A. (2015) · PLoS ONE · doi:10.1371/journal.pone.0125201 · Cited by 70 · see citing works
The whole-genome panorama of cancer driversPreprint
Sabarinathan, R., Pich, O., Martincorena, I., Rubio-Pérez, C., Juul, M., Wala, J. A., Schumacher, S. E., Shapira, O., Sidiropoulos, N., Waszak, S. M., et al. (2017) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/190330 · Cited by 55 · see citing works
Self-citationCytogenetic Analysis of Colorectal Adenomas
Ousager, L. B., Bardi, G., Pandis, N., Fenger, C., Kronborg, O., & Heim, S. (1998) · Cancer Genetics and Cytogenetics · doi:10.1016/s0165-4608(98)00047-8 · Cited by 44 · see citing works
Stamp, C., Županič, A., Sachdeva, A., Stoll, E. A., Shanley, D. P., Mathers, J. C., Kirkwood, T. B. L., Heer, R., Simons, B. D., Turnbull, D. M., et al. (2018) · EBioMedicine · doi:10.1016/j.ebiom.2018.04.017 · Cited by 23 · see citing works
Lugli, N., Dionellis, V. S., Ordóñez‐Morán, P., Kamileri, I., Sotiriou, S. K., Huelsken, J., & Halazonetis, T. D. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.05.051 · Cited by 21 · see citing works
Patterns of somatic genome rearrangement in human cancer
Roberts, N. D. (2018) · Apollo (University of Cambridge) · doi:10.17863/cam.22674 · Cited by 10 · see citing works
Boot, A., Ng, A. W. T., Chong, F. T., Ho, S.-C., Yu, W., Tan, D. S.-W., Iyer, N. G., & Rozen, S. (2018) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/368753 · Cited by 6 · see citing works
Abstract 970: The mutational landscape of normal human endometrial epithelium
Moore, L., Leongamornlert, D. A., Coorens, T. H. H., et al. (2019) · Tumor Biology · doi:10.1158/1538-7445.sabcs18-970 · Cited by 4 · see citing works
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Mutational signature in colorectal cancer caused by genotoxic pks+ E. coli
Pleguezuelos-Manzano, C., Puschhof, J., Rosendahl Huber, A., van Hoeck, A., Wood, H. M., Nomburg, J., Gurjao, C., Manders, F., Dalmasso, G., Stege, P. B., et al. (2020) · Nature · doi:10.1038/s41586-020-2080-8 · Cited by 1,208 · see citing works
The evolutionary history of 2,658 cancers
Gerstung, M., Jolly, C., Leshchiner, I., Dentro, S. C., Gonzalez, S., Rosebrock, D., Mitchell, T. J., Rubanova, Y., Anur, P., Yu, K., et al. (2020) · Nature · doi:10.1038/s41586-019-1907-7 · Cited by 1,057 · see citing works
Self-citationThe mutational landscape of normal human endometrial epithelium
Moore, L., Leongamornlert, D., Coorens, T. H. H., Sanders, M. A., Ellis, P., Dentro, S. C., Dawson, K. J., Butler, T., Rahbari, R., Mitchell, T. J., et al. (2020) · Nature · doi:10.1038/s41586-020-2214-z · Cited by 499 · see citing works
Self-citationAgeing and rejuvenation of tissue stem cells and their niches
Brunet, A., Goodell, M. A., & Rando, T. A. (2023) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-022-00510-w · Cited by 407 · see citing works
The mutational footprints of cancer therapies
Pich, O., Muiños, F., Lolkema, M. P., Steeghs, N., Gonzalez-Perez, A., & Lopez-Bigas, N. (2019) · Nature Genetics · doi:10.1038/s41588-019-0525-5 · Cited by 309 · see citing works
Extensive heterogeneity in somatic mutation and selection in the human bladder
Lawson, A. R. J., Abascal, F., Coorens, T. H. H., Hooks, Y., O’Neill, L., Latimer, C., Raine, K., Sanders, M. A., Warren, A. Y., Mahbubani, K. T. A., et al. (2020) · Science · doi:10.1126/science.aba8347 · Cited by 311 · see citing works
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Williams, N., Lee, J., Mitchell, E., Moore, L., Baxter, E. J., Hewinson, J., Dawson, K. J., Menzies, A., Godfrey, A. L., Green, A. R., et al. (2022) · Nature · doi:10.1038/s41586-021-04312-6 · Cited by 285 · see citing works
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Flanagan, D. J., Pentinmikko, N., Luopajärvi, K., Willis, N. J., Gilroy, K., Raven, A. P., Mcgarry, L., Englund, J. I., Webb, A. T., Scharaw, S., et al. (2021) · Nature · doi:10.1038/s41586-021-03525-z · Cited by 255 · see citing works
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Miller, M. B., Huang, A. Y., Kim, J., Zhou, Z., Kirkham, S. L., Maury, E. A., Ziegenfuss, J. S., Reed, H. C., Neil, J. E., Rento, L., et al. (2022) · Nature · doi:10.1038/s41586-022-04640-1 · Cited by 223 · see citing works
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Cook, J. H., Melloni, G. E. M., Gulhan, D. C., Park, P. J., & Haigis, K. M. (2021) · Nature Communications · doi:10.1038/s41467-021-22125-z · Cited by 208 · see citing works
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Li, R., Du, Y., Chen, Z., Xu, D., Lin, T., Jin, S., Wang, G., Liu, Z., Lu, M., Chen, X., et al. (2020) · Science · doi:10.1126/science.aba7300 · Cited by 206 · see citing works
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Self-citationMutagenesis by Microbe: the Role of the Microbiota in Shaping the Cancer Genome
Barrett, M., Hand, C. K., Shanahan, F., Murphy, T., & O’Toole, P. W. (2020) · Trends in Cancer · doi:10.1016/j.trecan.2020.01.019 · Cited by 108 · see citing works
Luquette, L. J., Miller, M. B., Zhou, Z., Bohrson, C. L., Zhao, Y., Jin, H., Gulhan, D., Ganz, J., Bizzotto, S., Kirkham, S., et al. (2022) · Nature Genetics · doi:10.1038/s41588-022-01180-2 · Cited by 108 · see citing works
Rouhani, F. J., Zou, X., Danecek, P., Badja, C., Amarante, T. D., Koh, G., Wu, Q., Memari, Y., Durbin, R., Martincorena, I., et al. (2022) · Nature Genetics · doi:10.1038/s41588-022-01147-3 · Cited by 105 · see citing works
Rosendahl Huber, A., Pleguezuelos-Manzano, C., Puschhof, J., Ubels, J., Boot, C., Saftien, A., Verheul, M., Trabut, L. T., Groenen, N., van Roosmalen, M., et al. (2024) · Cancer Cell · doi:10.1016/j.ccell.2024.02.009 · Cited by 106 · see citing works
Nougayrède, J.-P., Chagneau, C. V., Motta, J.-P., Bossuet-Greif, N., Belloy, M., Taieb, F., Gratadoux, J.-J., Thomas, M., Langella, P., & Oswald, E. (2021) · mSphere · doi:10.1128/msphere.00624-21 · Cited by 82 · see citing works
Clonal hematopoiesis and inflammation – the perpetual cycle
Avagyan, S., & Zon, L. I. (2023) · Trends in Cell Biology · doi:10.1016/j.tcb.2022.12.001 · Cited by 79 · see citing works
Contribution of pks+ E. coli mutations to colorectal carcinogenesis
Chen, B., Ramazzotti, D., Heide, T., Spiteri, I., Fernandez-Mateos, J., James, C., Magnani, L., Graham, T. A., & Sottoriva, A. (2023) · Nature Communications · doi:10.1038/s41467-023-43329-5 · Cited by 74 · see citing works
“Both distant and adjacent normal contained some driver mutations, aspreviously reported 9 (Fig.”
InfluentialGenetic Alterations of Metastatic Colorectal Cancer
Testa, U., Castelli, G., & Pelosi, E. (2020) · Biomedicines · doi:10.3390/biomedicines8100414 · Cited by 44 · see citing works
Microbiota and colorectal cancer: colibactin makes its mark
Arthur, J. C. (2020) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-020-0303-y · Cited by 30 · see citing works
Mäklin, T., Taira, A., Arredondo-Alonso, S., Shao, Y., Stratton, M. R., Lawley, T. D., Aaltonen, L. A., & Corander, J. (2025) · The Lancet Microbe · doi:10.1016/j.lanmic.2024.101015 · Cited by 22 · see citing works
Self-citationTerlouw, D., Boot, A., Ducarmon, Q. R., Nooij, S., Suerink, M., van Leerdam, M. E., van Egmond, D., Tops, C. M., Zwittink, R. D., Ruano, D., et al. (2024) · BMC Cancer · doi:10.1186/s12885-024-11849-y · Cited by 15 · see citing works
PKD1 mutant clones within cirrhotic livers inhibit steatohepatitis without promoting cancer
Zhu, M., Wang, Y., Lu, T., Guo, J., Li, L., Hsieh, M.-H., Gopal, P., Han, Y., Fujiwara, N., Wallace, D. P., et al. (2024) · Cell Metabolism · doi:10.1016/j.cmet.2024.05.015 · Cited by 9 · see citing works
Ren, P., Zheng, C., Pang, Y., Qiang, Y., Sun, S., Wang, Q., Xu, W., Lee, M., Lu, Z., Zhou, M., et al. (2025) · Nature Aging · doi:10.1038/s43587-025-01011-z · Cited by 6 · see citing works
Di Pierro, F., Sagheddu, V., Galletti, S., Casaroli, A., Labrini, E., Soldi, S., Cazzaniga, M., Bertuccioli, A., Matera, M., Cavecchia, I., et al. (2026) · Probiotics and Antimicrobial Proteins · doi:10.1007/s12602-025-10522-5 · Cited by 5 · see citing works
“It is worth remembering that cancer research suggests that colibactin causes DNA damage early after exposure [157, 158].”
- Authors
- Lee-Six, H., Olafsson, S., Ellis, P., Osborne, R. J., Sanders, M. A., Moore, L., Georgakopoulos, N., Torrente, F., Noorani, A., Goddard, M., Robinson, P., Coorens, T. H. H., O’Neill, L., Alder, C., Wang, J., Fitzgerald, R. C., Zilbauer, M., Coleman, N., Saeb-Parsy, K., Martincorena, I., Campbell, P. J., & Stratton, M. R.
- Affiliations
- Wellcome Sanger Institute (GB)
- Erasmus MC (NL)
- University of Cambridge (GB)
- Addenbrooke's Hospital (GB)
- Royal Papworth Hospital (GB)
- Corresponding author
- Stratton, Michael R.
- ORCID
- Venue
- Nature
- Published
- 2019-10-23
- Volume
- 574
- Issue
- 7779
- Pages
- 532-537
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2981552021
- Cited by
- 747
- References
- 60
- Citations by year
- 2026: 78 · 2025: 98 · 2024: 93 · 2023: 111 · 2022: 135 · 2021: 120 · 2020: 93 · 2019: 18 · 2018: 1
- FWCI
- 28.95
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- Funders
- European Hematology Association (TRTH182)
- Wellcome Trust (103858/Z/14/Z)
- Cancer Research UK (S_3369, 21777)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
- Health Sciences › Medicine › Oncology › Colorectal Cancer Screening and Detection
- Keywords
- somatic mutations, colorectal epithelium, colonic crypts, mutational signatures, mutational processes, driver mutations, colorectal adenoma-carcinoma sequence, mutational burden, clonal evolution, normal tissue, colorectal cancer
- MeSH terms
- Adenoma, Aged, Carcinoma, Cell Transformation, Neoplastic, Clone Cells, Colon, DNA Mutational Analysis, Epithelial Cells, Female, Humans, Intestinal Mucosa, Male, Middle Aged, Mutation, Rectum, Stem Cells, Colorectal Neoplasms, DNA Copy Number Variations, Axin Protein, Prodromal Symptoms
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